Numb endocytic adaptor protein (NUMB)

The Numb endocytic adaptor protein (NUMB) is a multi-domain, evolutionarily conserved protein that orchestrates a diverse range of cellular processes. Its best-characterized roles include acting as a cargo-selective endocytic adaptor in clathrin-mediated endocytosis and as a major antagonist of Notch receptor signaling, primarily regulating cell fate during asymmetric division and stem cell maintenance[1][2][3][5]. NUMB functions by binding diverse protein partners via its PTB (phosphotyrosine-binding) and PRR (proline-rich region) domains, anchoring endocytic and signaling complexes at the plasma membrane, and regulating the endocytosis of key receptors such as integrins, E-cadherin, and TrkB[2][3][1]. NUMB also acts as a scaffold for E3 ligases like Itch in the targeted ubiquitination and degradation of Notch and other signaling proteins[3]. Through these multifaceted interactomes and regulatory actions, NUMB critically modulates developmental processes, cell migration, adhesion, tumorigenesis, and neural function. Loss or dysregulation of NUMB is implicated in oncogenic transformation, cancer progression, and developmental abnormalities[2][3][5].

Other names

Protein numb homologC14orf41h-NumbProtein S171S171c14_5527numb homologLOC101928143

Indirect Notch pathway inhibition or modulation—pharmacologically targeting downstream or upstream elements of the NUMB/Notch axis (e.g., γ-secretase inhibitors for Notch); Restoration of NUMB function or stabilization—considered as a strategy in some cancer models; not yet clinically established.